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M Bessho

Publications and source records attributed to M Bessho.

At least 73 records · Page 4Linked to original sources
PubMed1994

Acute ischaemic preconditioning and chronic hypoxia independently increase myocardial tolerance to ischaemia.

OBJECTIVE: Myocardial adaptation has been reported to result from mild but chronic ischaemia in the hearts of patients with coronary artery disease. The aim of this study was to test the hypothesis that the responses of the chronically hypoxic myocardium to an episode of severe ischaemia, or the effects of acute ischaemic preconditioning on myocardial function after subsequent fatal ischaemia, may differ between the normoxic and the chronically hypoxic myocardium. METHODS: A rat model of three week hypoxia (10% O2) was used to simulate tissue hypoxia caused by chronic ischaemia. In isolated isovolumetrically contracting hearts perfused with oxygenated erythrocyte-containing Tyrode solution, systolic and diastolic functions during a 15 or 20 min period of ischaemia and reperfusion were measured in the normoxic control and chronically hypoxic groups. RESULTS: Increases in diastolic pressure during ischaemia were smaller and the recovery of developed pressure during reperfusion was greater in the chronically hypoxic group than in the normoxic group. The hearts of the normoxic group never recovered from ischaemic damage after 20 min ischaemia. The beneficial effects of acute preconditioning with 5 min ischaemia on myocardial function were observed after 15 min ischaemia in the normoxic group, and during and after 20 min ischaemia in the chronically hypoxic group. Changes in lactate production and high energy phosphates could not explain the increased tolerance to ischaemia in the chronically hypoxic group. CONCLUSIONS: Chronic hypoxia increased myocardial tolerance to ischaemia, and acute ischaemic preconditioning increased the tolerance further. Thus chronic hypoxia and acute ischaemic preconditioning independently activate protective mechanisms against ischaemia; the mechanisms may differ between the two types of insult.

Acute Disease↗
PubMed1994

Relationship of blood flow to antral lesion incidence in rat gastric mucosa after hemorrhage and retransfusion.

The relationship of gastric mucosal hemodynamics, energy metabolism, and acid to antral histological lesion incidence following hemorrhage and retransfusion was investigated in rats. Decrease of mucosal blood flow and of the index of mucosal oxygen saturation (ISO2) during hemorrhage were slightly greater in the corpus than in the antrum. ATP content and redox ratio in the corpus were decreased by shock; however, these hardly changed in the antrum. The index of tissue hemoglobin concentration (IHb) recovered to above the prehemorrhage value only in the antrum after retransfusion. Histological lesion incidence in the antral mucosa was more markedly increased by acid instillation and/or retransfusion than in the corpus. From these results, it was concluded that the decrease of blood flow is related as an underlying factor to induction of ischemic damage in the antral mucosa and that intraluminal acid and/or postischemic hyperemia play a causative role in the development of histologic lesions in the antral mucosa during shock and retransfusion in the rat stomach.

Adenine Nucleotides↗
PubMed1994

Effects of menatetrenone on the decrease in calcium balance induced by vitamin K-deficient diet and sodium loading in rats.

The effects of menatetrenone (2-methyl-3-tetraprenyl-1,4-naphthoquinone, MK-4) on calcium balance were studied in male Sprague-Dawley rats. Experiment 1: Rats in metabolic cages that were fed a vitamin K-deficient diet and injected daily with latamoxef (100 mg/kg, i.p.) were either treated or untreated with MK-4 for 7 days. Daily food intake, urine volume and feces weight were determined, and calcium concentration in these samples was measured. Calcium balance was calculated as the difference between calcium intake and urinary and fecal calcium excretion. Cumulative calcium balance in the vitamin K-deficient group treated with latamoxef was lower than that in normal rats; this balance was significantly improved by MK-4 (1 and 10 mg/kg, s.c.) administered for 7 days. Experiment 2: Rats were fed a vitamin K-deficient diet containing 4.6% sodium chloride for 6 weeks. MK-4 was administered as a dietary supplement. Forty-eight-hour calcium balance, determined once a week, was significantly reduced compared with that of normal rats after 3 and 5 weeks; the balance was restored dose-dependently by MK-4 administration (1 and 10 mg/kg). Experiment 3: Rats were subjected to the same experimental conditions as experiment 2 for 6 weeks, and intestinal calcium transport was determined using an everted gut-sac technique. Calcium transport was reduced by the high sodium, vitamin K-deficient diet, and this reduction was restored by MK-4 administration (10 mg/kg). These results suggest that MK-4 improves the reduced calcium balance by increasing intestinal calcium absorption in these rats.

Alkaline Phosphatase↗
PubMed1994

Suppression of the development of murine myeloid leukemia with granulocyte colony-stimulating factor by inducing apoptosis of leukemic cells.

We studied the antileukemic effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) by using a radiation-induced murine myeloid leukemia cell line C2M-A5. Intravenous inoculation of C2M-A5 cells into C3H/He mice resulted in the development of myeloid leukemia. However, the leukemic death of the mice was completely suppressed by the subcutaneous injections of rhG-CSF. In order to clarify the mechanism of the suppression, effects of rhG-CSF on C2M-A5 cells were studied in vitro. While C2M-A5 cells grew exponentially in the absence of rhG-CSF, the viability, the growth, and the self-renewal capacity of C2M-A5 cells were all suppressed in cultures in the presence of rhG-CSF. Preincubation with rhG-CSF for 48 h deprived C2M-A5 cells of the ability to induce leukemia in syngeneic mice. Morphological examination revealed the appearance of apoptotic changes of C2M-A5 cells in cultures containing rhG-CSF over the 2-day incubation period. In gel electrophoresis, the DNA from C2M-A5 cells incubated with rhG-CSF for 48 h showed a ladder of degradated DNA bands compatible with apoptosis. From these results, we concluded that the apoptosis of C2M-A5 cells played a key role in the antileukemic effect of rhG-CSF.

Animals↗
PubMed1993

Increased tolerance of ventricular function and energy metabolism to hypoxia in cardiomyopathic hamsters.

To study the responses of myocardial function and metabolism to hypoxia in normal hamsters and cardiomyopathic hamsters (Bio 14.6), left ventricular pressure was measured in an isolated isovolumically beating heart preparation, and myocardial high energy phosphates (ATP and creatine phosphate), inorganic phosphate, and intracellular pH were also measured by 31P nuclear magnetic resonance spectroscopy. In 20-week-old cardiomyopathic hamsters, the heart weight was increased and the baseline left ventricular developed pressure, peak positive dP/dt, and peak negative dP/dt were decreased, indicating depression of left ventricular function. In control hamsters, left ventricular end-diastolic pressure rose markedly (+481 +/- 70%), and left ventricular developed pressure decreased (-57 +/- 6%) during 30 mins period of hypoxic perfusion. Correspondingly, myocardial content of ATP (-42 +/- 17%) and creatine phosphate (-48 +/- 14%) was decreased and that of inorganic phosphate was increased (+185 +/- 127%). Intracellular pH was also decreased (-0.20 +/- 0.13). In contrast, cardiomyopathic hamsters, showed a relatively slight increase in left ventricular end-diastolic pressure (+106 +/- 83%, P < 0.01 vs. control hamsters), although the decrease in left ventricular developed pressure (-50 +/- 5%) was comparable to that in control hamsters. The recovery of left ventricular end-diastolic pressure and developed pressure during reoxygenation was better in cardiomyopathic hamsters. The decrease in myocardial ATP (-13 +/- 26%, P < 0.01 vs. control hamsters), the increase in inorganic phosphate (+95 +/- 88%, P < 0.05 vs. control hamsters), and the decrease in intracellular pH (-0.06 +/- 0.06, P < 0.01 vs. control hamsters) during hypoxia were much less marked in cardiomyopathic hamsters. Only the decrease in creatine phosphate (-32 +/- 16%) was comparable to that in control hamsters. Thus, in cardiomyopathic hamsters, the deterioration of left ventricular diastolic function, systolic function, and myocardial energy metabolism during hypoxia was mild compared with the change in control healthy hamsters. This increased tolerance of cardiomyopathic hearts to hypoxia may be related to alterations in myocardial contractile proteins and/or energy utilization, or substrate availability.

Animals↗
PubMed1993

A clonal study of hematopoiesis using the M27 beta probe: aberrant band patterns caused by incomplete digestion of a methyl-sensitive enzyme in the the inactive X-chromosome.

The M27 beta probe has been used to determine the clonality of human tumors, based upon X-chromosome inactivation. However, it occasionally gives rise to aberrant results. In this study, the M27 beta probe was used for clonal analysis in Japanese women with clonal stem cell disorders and in those with normal hematopoiesis. Restriction digestion with PstI indicated heterozygosity for the DXS255 locus in 41 out of 50 individuals (82%). Further digestion with HpaII in heterozygous women led to four distinct band patterns: I, both fragments were partially digested; II, either one of the two fragments was completely digested; III, a three-band pattern; and IV, neither fragment was digested. Of 21 hematologically normal females, 17 (81%) and four (19%) had patterns I and III, respectively. In some subjects with pattern I, imbalanced HpaII digestion in the two alleles was seen. Fifteen (65%) of the 23 patients with clonal stem cell disorders had pattern II, while the remainder (35%) had pattern IV. The normal tissues of three acute myeloid leukemia patients with pattern IV all revealed pattern I. It is possible that the aberrant band patterns could be caused by incomplete HpaII digestion in inactive X-chromosomes. In this study, we propose a hypothesis whereby, in normal tissues, aberrant cells, the DXS255 locus of which is not digested with HpaII despite their inactive status, would be mixed with cells demonstrating the usual methylation pattern. In normal tissues, complex of proportion of aberrant cells and skewed Lyonization could produce a variety of band patterns. If a cell with the usual methylation pattern proliferated monoclonally, pattern II would be seen: whereas if an aberrant cell proliferated, pattern IV would be demonstrated.

Blotting, Southern↗
PubMed1992

A hematological remission by clonal hematopoiesis after treatment with recombinant human granulocyte-macrophage colony-stimulating factor and erythropoietin in a patient with therapy-related myelodysplastic syndrome.

We treated a patient with therapy-related myelodysplastic syndrome (MDS) with human recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) and erythropoietin (Epo). The patient achieved a hematological remission which continued for more than 16 months despite discontinuation of the treatment. Before the treatment with GM-CSF and Epo the patient had severe pancytopenia, required frequent red cell transfusions, and experienced episodes of severe infection, but after the therapy he no longer needed transfusion and no longer had the infection. While the patient remained in hematological remission, bone marrow examination revealed trilineage dysplasia, and cytogenetic analysis showed an abnormal karyotype [48, XY, +8, +der(1q5p)] in 100% of the metaphases examined. These findings suggest that the hematological remission of this patient may not result from the recovery of the non-clonal hematopoiesis of a normal clone, but result from the monoclonal hematopoiesis of a neoplastic clone.

Blood Cell Count↗
PubMed1992

Interleukin-6 reduces the optimal growth in vitro of leukemic blast progenitors from acute myeloblastic leukemia patients.

The combined effects of five cytokines; recombinant human (rHu) granulocyte colony-stimulating factor (G-CSF), rHu granulocyte-macrophage colony-stimulating factor (GM-CSF), rHu interleukin-1 beta (IL-1 beta), rHu interleukin-3 (IL-3), and rHu interleukin-6 (IL-6) on blast colony formation in methylcellulose by leukemic blast progenitors from 10 patients with acute myeloblastic leukemia (AML) were studied. Combination of G-CSF, GM-CSF, IL-1 beta, and IL-3 stimulated maximum blast colony formation in 9 patients. Further addition of IL-6 reduced the combined effect of the four cytokines on blast colony formation. IL-6 regulates the proliferation of leukemic blast progenitors and may play an important role in the regulation of hematopoiesis.

Bone Marrow↗
PubMed1992

[Regulation of proliferation and differentiation of hematopoietic cells by cytokines].

Recent studies on the hematopoietic system have revealed that both constitutive and inducible hematopoiesis are regulated by complicated networks composed of various kinds of cytokines and that there are some general rules for hematopoietic cytokine biology. Further accumulation of knowledge about the regulation of proliferation and differentiation of hematopoietic cells by cytokines will serve to clarify the pathophysiology of hematological diseases, resulting in the development of therapeutic strategy for these diseases.

Cell Differentiation↗
PubMed1992

[Hairy cell leukemia successfully treated with deoxycoformycin].

A 45-year-old male was hospitalized on September 2, 1989 with chief complaints of general fatigue and fever. Physical examination revealed hepatomegaly and massive splenomegaly. Laboratory tests on admission showed Hb of 7.5g/dl, PLT 4.8 x 10(4)/microliters and WBC 9,610/microliters with 81% hairy cells. Bone marrow aspirate demonstrated 55.1% hairy cells and moderate myelofibrosis. Cytochemically, hairy cells were positive for tartrate-resistant acid phosphatase (TRAP). Surface markers were SmIg G+ A+ kappa +, CD11b+, CD11c+, CD19+, CD20+, CD21-, CD25+, HC2+, HLA-DR+. From these findings, a diagnosis of hairy cell leukemia (HCL) was made. After administration of deoxycoformycin (DCF) at a dose of 5.0mg/m2 1-2 times monthly, splenomegaly disappeared, as did hairy cells from the peripheral blood. Hematological level returned to within normal range except for the presence of 1.2% hairy cells and mild myelofibrosis in bone marrow aspirates. DCF has so far been effective for this patient. While DCF has been reported to be effective in the treatment of HCL in the West, it has not been determined in Japanese patients with HCL, who have different hematologic features from those of HCL patients in the West.

Humans↗
PubMed1991

Enhancement by transforming growth factor-beta 1 (TGF-beta 1) of the proliferation of leukemic blast progenitors stimulated with IL-3.

We studied the effect of transforming growth factor-beta 1 (TGF-beta 1) on colony formation of leukemic blast progenitors from ten acute myeloblastic leukemia (AML) patients stimulated with granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), interleukin-6 (IL-6), or interleukin-1 beta (IL-1 beta). These CSFs and interleukins by themselves stimulated the proliferation of leukemic blast progenitors without adding TGF-beta 1. G-CSF, GM-CSF, and IL-3 stimulated blast colony formation in nine patients, IL-6 stimulated it in five, and IL-1 beta stimulated in four. TGF-beta 1 significantly reduced blast colony formation stimulated by G-CSF, GM-CSF, or IL-6 in all patients. In contrast, TGF-beta 1 enhanced the stimulatory effect of IL-3 on blast progenitors from three cases, while in the other seven patients TGF-beta 1 reduced blast colony formation in the presence of IL-3. To study the mechanism by which TGF-beta 1 enhanced the stimulatory effect of IL-3 on blast progenitors, we carried out the following experiments in the three patients in which it occurred. First, the media conditioned by leukemic cells in the presence of TGF-beta 1 stimulated the growth of leukemic blast progenitors, but such effect was completely abolished by anti-IL-1 beta antibody. Second, the addition of IL-1 beta in the culture significantly enhanced the growth of blast progenitors stimulated with IL-3. Third, leukemic cells of the two patients studied were revealed to secrete IL-1 beta and tumor necrosis factor-alpha (TNF-alpha) constitutively; the production by leukemic cells of IL-1 beta and TNF-alpha was significantly promoted by TGF-beta 1. Furthermore, the growth enhancing effect of TGF-beta 1 in the presence of IL-3 was fully neutralized by anti-IL-1 beta antibody. These findings suggest that TGF-beta 1 stimulated the growth of blast progenitors through the production and secretion of IL-1 beta by leukemic cells.

Aged↗
PubMed1991

Differential extractability of creatine phosphate and ATP from cardiac muscle with ethanol and perchloric acid solution.

To compare the extractability of creatine phosphate with that of ATP by alcohol extraction, both compounds were extracted from normal perfused rat heart tissues by using various stepwise concentrations of ethanol and 0.4 M HClO4. Powdered samples (6-15 mg wet wt) from the freeze-clamped tissues were homogenized in 2 ml of the ethanol solutions. After centrifugation, the supernatant was removed; each centrifuged sediment was rehomogenized with 2 ml of 0.4 M HClO4 and centrifuged. The supernatant was neutralized with 0.4 m KHCO3. The same powdered samples were directly homogenized with 2 ml of 0.4 M HClO4 and treated in the same manner. Only a small amount of ATP in the tissues was extracted by an 85% or higher concentration of ethanol. Further, about 13% of the tissue ATP was not extractable by the subsequent perchloric acid extraction. In contrast to ATP, creatine phosphate in the tissues was partially extracted by 95% ethanol and nearly all of the tissue creatine phosphate was extracted by 70% ethanol. The total creatine phosphate obtained by 70% ethanol and by subsequent perchloric acid extraction was significantly higher than that obtained by direct perchloric acid extraction. From these results, it was concluded that the extractability of creatine phosphate in the tissue by alcohol extraction is clearly different from that of ATP. Additionally, the stepwise extraction is recommended as a useful method for the extraction of energy metabolites in perfused rat heart tissue.

Adenosine Triphosphate↗
PubMed1991

Long survival of leukemic mice by repeated combination treatment of cyclophosphamide and recombinant human granulocyte colony-stimulating factor.

The therapeutic and hematological effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) in combination with cyclophosphamide (CY) were investigated in a murine myeloid leukemia model. Ten daily administrations of rhG-CSF following CY prolonged the survival time of leukemic mice more than either agent alone. Hematological examination indicated that this effect was attributable to suppression with rhG-CSF of the leukemic repopulation after CY injection. In addition, rhG-CSF accelerated recovery from CY-induced neutropenia. Based on these hematological changes, a treatment regimen was established consisting of a single injection of CY on day 1 and daily injections of rhG-CSF on days 2-6; this combination treatment was given to the leukemic mice for up to four cycles, with a pause of one day between each cycle. The leukemic mice completed each cycle of treatment with few failures, and it resulted in a long survival time for the leukemic mice. The mean survival time of the mice receiving four cycles of treatment was 47 days, 30 days longer than that of the untreated mice. Hematological examination performed at the end of each cycle showed that the leukemic cell population was controlled at a level equal to or below the pre-treatment level, and peripheral blood neutrophils were maintained at a level equal to or above the normal level. These results indicate the possible effectiveness of combining rhG-CSF with chemotherapeutic drugs in controlling leukemic cell growth, and the effectiveness of rhG-CSF in enhancing neutrophil recovery after chemotherapy. However, it was found that the leukemic cells became resistant to treatment with rhG-CSF after four cycles of combination treatment, suggesting that great care should be taken in the clinical application of rhG-CSF, even when the growth of acute myelogenous leukemia cells is not apparently stimulated by it.

Animals↗
PubMed1991

[Clinical features of atypical refractory anemia (RA)].

Twenty-three patients with bicytopenia or pancytopenia were retrospectively studied. The patients with underlying disorders, blast count of more than 5% on bone marrow (BM) aspirate, blast count of more than 1% on peripheral blood or ringed sideroblast count of more than 15% on BM aspirate were excluded. According to Yoshida's criteria, 23 patients were classified into 6 subtypes [AA (aplastic anemia)1: typical AA, AA2: atypical AA, MDS (myelodysplastic syndrome)3: typical RA (refractory anemia, MDS4-6: atypical RA], and AA1 7 cases; AA2 2 cases; MDS3 5 cases; MDS4 1 case; MDS5 2 cases; MDS6 6 cases. To clarify the clinical features of atypical RA group (MDS4-6), we investigated ferrokinetics, RBC life span, karyotype, serum Epo (erythropoietin) concentration, response to therapy and prognosis. Results were as follows: 1) all three RA patients who were younger than 30 years old were included in atypical RA group, 2) in ferrokinetics study PID (plasma iron disappearance time) values of MDS4 and MDS6 patients ranged between those of AA1 and those of MDS3 patients (5 of 7 patients), 3) two cases who developed leukemia belonged to typical RA group, 4) patients with atypical RA showed response to therapy and their prognosis were better than those with typical RA. These observations suggest that atypical RA have different clinical features from typical RA.

Adolescent↗
PubMed1990

Transformation of bilineal hybrid acute leukemia to acute lymphoid leukemia: a case report with serial analyses of cytogenetics and gene rearrangement.

A 17-year-old male with bilineal hybrid acute leukemia is described. Two-color flow cytometric analysis of blast surface phenotype revealed that there were two groups of blasts which showed either CD 10+ CD 19+ CD 13- CD 33- or CD 10- CD 19- CD 13+ CD 33+, but not both. He developed a complete remission by treatment with vincristine, prednisolone, adriamycin, and L-asparaginase. After 8 months, however, leukemia relapsed and lymphoid blasts were dominant. Cytogenetic analysis at presentation showed 46,XY,t(3;9)(p21;p22), and at relapse it showed 46,XY,t(1;3;9)(1pter----1q32::3p25----3pter;3 qter----3p21::9p22----9pter; 9qter----9p22::3p21----3p25::1q32----1q ter),t(2;19)(p21;q13). Analysis of the heavy chain joining region at diagnosis showed three hybridizing bands, all rearranged, but at relapse only one rearranged band. Analysis of the constant region for the beta T-cell receptor gene (TCR beta) both at diagnosis and at relapse showed one rearranged and one germline band, suggesting that rearrangement of one allele of TCR beta of not only lymphoid but also myeloid blasts occurred. It is considered that the target cell of lymphoid leukemia cells and that of myeloid leukemia cells at diagnosis were the same, which differentiated to two lineages, and the clone which evolved from lymphoid lineage proliferated at relapse.

Adolescent↗
PubMed1990

Improvement of anemia by recombinant erythropoietin in patients with myelodysplastic syndromes and aplastic anemia.

Eight patients with myelodysplastic syndromes (MDS) and four patients with aplastic anemia (AA) were treated with recombinant erythropoietin (rEpo) to investigate its effect on the anemia of these patients. rEpo was administered by i.v. injection three times a week for at least four weeks. The doses were 3,000, 6,000, or 12,000 U/day. Despite an elevated "endogenous" Epo level, a greater than 1.5 g/dl increase in hemoglobin (Hb) concentration was observed in one patient with refractory anemia (RA), one patient with refractory anemia with excess of blasts (RAEB), and one patient with AA. A greater than 50% decrease in red cell transfusion requirement was observed in one patient with RA and one patient with AA. One RA patient and one AA patient have received rEpo as maintenance therapy for more than 64 and 100 weeks, respectively. They no longer need red cell transfusions and have had a normal Hb concentration and normal ferrokinetics. No side effect was seen. These results indicate that rEpo may benefit some patients with MDS and AA who are dependent on red cell transfusions while further studies will be necessary to elucidate the mechanism by which rEpo stimulates erythropoiesis and improves anemia in patients with these diseases.

Adult↗